Neuroanatomical and prognostic associations of depression in Parkinson's disease.

BACKGROUND: Depression is reported as a risk factor, prodromal feature and late consequence of Parkinson's disease (PD). We aimed to evaluate the timing, neuroanatomy and prognostic implications of depression in PD. METHODS: We used data from 434 023 participants from UK Biobank with 14.1 years of follow-up. Multivariable regression models established associations of depression with incident PD and regional brain volumes. Cox proportional hazards models assessed prognostic associations of depression in PD with incident dementia and all-cause mortality. RESULTS: Of 2632 individuals with incident PD, 539 (20.5%) were diagnosed with depression at some point. Depression was associated with an increased risk of subsequent PD (risk ratio 1.53, 95% CI 1.37 to 1.72). Among incident PD cases, depression prevalence rose progressively from 10 years pre-PD diagnosis (OR 2.10, 95% CI 1.57 to 2.83) to 10 years postdiagnosis (OR 3.51, 95% CI 1.33 to 9.22). Depression severity in PD was associated with reduced grey matter volume in structures including the thalamus and amygdala. Depression prior to PD diagnosis increased risk of dementia (HR 1.47, 95% CI 1.05 to 2.07) and mortality (HR 1.30, 95% CI 1.07 to 1.58). CONCLUSIONS: This large-scale prospective study demonstrated that depression prevalence increases from 10 years before PD diagnosis and is a marker of cortical and subcortical volume loss. Depression before PD diagnosis signals a worse prognosis in terms of dementia and mortality. This has clinical implications in stratifying people with poorer cognitive and prognostic trajectory in PD.

AccessPD as a next generation registry to accelerate Parkinson's disease research.

Recruitment is a major rate-limiting factor in Parkinson's disease (PD) research. AccessPD is a unique platform that aims to create a registry of more than 2000 PD patients and a rich database of PD-relevant information. Potential participants are identified using electronic health records (EHRs) in primary care. They are contacted via text message with an individualized link to the study portal. Electronic patient-reported outcomes (ePRO) are collected via online questionnaires and integrated with existing EHR. 200 participants were recruited within the first 6 months, of which 191 answered the follow-up questionnaire. Here, to showcase the potential of AccessPD, we described the most common diagnoses before and after PD diagnosis, the most commonly prescribed drugs, and identified participants who could benefit from device-aided therapies using consensus criteria. AccessPD shows its unique ability to link different data sources for patient stratification in longitudinal studies and recruitment into clinical trials.

The Motor Dysfunction Seen in Isolated REM Sleep Behavior Disorder.

BACKGROUND: Isolated Rapid Eye Movement (REM) sleep Behavior Disorder (iRBD) requires quantitative tools to detect incipient Parkinson's disease (PD). METHODS: A motor battery was designed and compared with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III) in people with iRBD and controls. This included two keyboard-based tests (BRadykinesia Akinesia INcoordination tap test and Distal Finger Tapping) and two dual tasking tests (walking and finger tapping). RESULTS: We included 33 iRBD patients and 29 controls. The iRBD group performed both keyboard-based tapping tests more slowly (P < 0.001, P = 0.020) and less rhythmically (P < 0.001, P = 0.006) than controls. Unlike controls, the iRBD group increased their walking duration (P < 0.001) and had a smaller amplitude (P = 0.001) and slower (P = 0.007) finger tapping with dual task. The combination of the most salient motor markers showed 90.3% sensitivity for 89.3% specificity (area under the ROC curve [AUC], 0.94), which was higher than the MDS-UPDRS-III (minus action tremor) (69.7% sensitivity, 72.4% specificity; AUC, 0.81) for detecting motor dysfunction. CONCLUSION: Speed, rhythm, and dual task motor deterioration might be accurate indicators of incipient PD in iRBD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

GBA1 rs3115534 Is Associated with REM Sleep Behavior Disorder in Parkinson's Disease in Nigerians.

BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) is an early feature of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Damaging coding variants in Glucocerebrosidase (GBA1) are a genetic risk factor for RBD. Recently, a population-specific non-coding risk variant (rs3115534) was found to be associated with PD risk and earlier onset in individuals of African ancestry. OBJECTIVES: We aimed to investigate whether the GBA1 rs3115534 PD risk variant is associated with RBD in persons with PD. METHODS: We studied 709 persons with PD and 776 neurologically healthy controls from Nigeria. All DNA samples were genotyped and imputed, and the GBA1 rs3115534 risk variant was extracted. The RBD screening questionnaire (RBDSQ) was used to assess symptoms of possible RBD. RESULTS: RBD was present in 200 PD (28.2%) and 51 (6.6%) controls. We identified that the non-coding GBA1 rs3115534 risk variant is associated with possible RBD in individuals of Nigerian origin (ß, 0.3640; standard error [SE], 0.103, P = 4.093e-04), as well as in all samples after adjusting for PD status (ß, 0.2542; SE, 0.108; P = 0.019) suggesting that although non-coding, this variant may have the same downstream consequences as GBA1 coding variants. CONCLUSIONS: Our results indicate that the non-coding GBA1 rs3115534 risk variant is associated with an increasing number of RBD symptoms in persons with PD of Nigerian origin. Further research is needed to assess if this variant is also associated with polysomnography-defined RBD and with RBD symptoms in DLB. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Nitrous oxide abuse direct measurement for diagnosis and follow-up: update on kinetics and impact on metabolic pathways.

Recreational use of nitrous oxide (N2O) has become a major health issue worldwide, with a high number of clinical events, especially in neurology and cardiology. It is essential to be able to detect and monitor N2O abuse to provide effective care and follow-up to these patients. Current recommendations for detecting N2O in cases of recreational misuse and consumption markers are lacking. We aimed to update current knowledge through a review of the literature on N2O measurement and kinetics. We reviewed the outcomes of experiments, whether in preclinical models (in vitro or in vivo), or in humans, with the aim to identify biomarkers of intoxication as well as biomarkers of clinical severity, for laboratory use. Because N2O is eliminated 5 min after inhalation, measuring it in exhaled air is of no value. Many studies have found that urine and blood matrices concentrations are connected to ambient concentrations, but there is no similar data for direct exposure. There have been no studies on N2O measurement in direct consumers. Currently, patients actively abusing N2O are monitored using effect biomarkers (biomarkers related to the effects of N2O on metabolism), such as vitamin B12, homocysteine and methylmalonic acid.

Estimating presymptomatic episodic memory impairment using simple hand movement tests: A cross-sectional study of a large sample of older adults.

INTRODUCTION: Finding low-cost methods to detect early-stage Alzheimer's disease (AD) is a research priority for neuroprotective drug development. Presymptomatic Alzheimer's is associated with gait impairment but hand motor tests, which are more accessible, have hardly been investigated. This study evaluated how home-based Tasmanian (TAS) Test keyboard tapping tests predict episodic memory performance. METHODS: 1169 community participants (65.8 ± 7.4 years old; 73% female) without cognitive symptoms completed online single-key and alternate-key tapping tests and episodic memory, working memory, and executive function cognitive tests. RESULTS: All single-key (R2 adj  = 8.8%, ΔAIC = 5.2) and alternate-key (R2 adj  = 9.1%, ΔAIC = 8.8) motor features predicted episodic memory performance relative to demographic and mood confounders only (R2 adj  = 8.1%). No tapping features improved estimation of working memory. DISCUSSION: Brief self-administered online hand movement tests predict asymptomatic episodic memory impairment. This provides a potential low-cost home-based method for stratification of enriched cohorts. HIGHLIGHTS: We devised two brief online keyboard tapping tests to assess hand motor function. 1169 cognitively asymptomatic adults completed motor- and cognitive tests online. Impaired hand motor function predicted reduced episodic memory performance. This brief self-administered test may aid stratification of community cohorts.

Modifiable risk factors for multiple sclerosis have consistent directions of effect across diverse ethnic backgrounds: a nested case-control study in an English population-based cohort.

BACKGROUND: Multiple sclerosis is a leading cause of non-traumatic neurological disability among young adults worldwide. Prior studies have identified modifiable risk factors for multiple sclerosis in cohorts of White ethnicity, such as infectious mononucleosis, smoking, and obesity during adolescence/early adulthood. It is unknown whether modifiable exposures for multiple sclerosis have a consistent impact on risk across ethnic groups. AIM: To determine whether modifiable risk factors for multiple sclerosis have similar effects across diverse ethnic backgrounds. METHODS: We conducted a nested case-control study using data from the UK Clinical Practice Research Datalink. Multiple sclerosis cases diagnosed from 2001 until 2022 were identified from electronic healthcare records and matched to unaffected controls based on year of birth. We used stratified logistic regression models and formal statistical interaction tests to determine whether the effect of modifiable risk factors for multiple sclerosis differed by ethnicity. RESULTS: We included 9662 multiple sclerosis cases and 118,914 age-matched controls. The cohort was ethnically diverse (MS: 277 South Asian [2.9%], 251 Black [2.6%]; Controls: 5043 South Asian [5.7%], 4019 Black [4.5%]). The age at MS diagnosis was earlier in the Black (40.5 [SD 10.9]) and Asian (37.2 [SD 10.0]) groups compared with White cohort (46.1 [SD 12.2]). There was a female predominance in all ethnic groups; however, the relative proportion of males was higher in the South Asian population (proportion of women 60.3% vs 71% [White] and 75.7% [Black]). Established modifiable risk factors for multiple sclerosis-smoking, obesity, infectious mononucleosis, low vitamin D, and head injury-were consistently associated with multiple sclerosis in the Black and South Asian cohorts. The magnitude and direction of these effects were broadly similar across all ethnic groups examined. There was no evidence of statistical interaction between ethnicity and any tested exposure, and no evidence to suggest that differences in area-level deprivation modifies these risk factor-disease associations. These findings were robust to a range of sensitivity analyses. CONCLUSIONS AND RELEVANCE: Established modifiable risk factors for multiple sclerosis are applicable across diverse ethnic backgrounds. Efforts to reduce the population incidence of multiple sclerosis by tackling these risk factors need to be inclusive of people from diverse ethnicities.

Gene-Environment Interactions for Parkinson's Disease.

OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disorder with complex etiology. Multiple genetic and environmental factors have been associated with PD, but most PD risk remains unexplained. The aim of this study was to test for statistical interactions between PD-related genetic and environmental exposures in the 23andMe, Inc. research dataset. METHODS: Using a validated PD polygenic risk score and common PD-associated variants in the GBA gene, we explored interactions between genetic susceptibility factors and 7 lifestyle and environmental factors: body mass index (BMI), type 2 diabetes (T2D), tobacco use, caffeine consumption, pesticide exposure, head injury, and physical activity (PA). RESULTS: We observed that T2D, as well as higher BMI, caffeine consumption, and tobacco use, were associated with lower odds of PD, whereas head injury, pesticide exposure, GBA carrier status, and PD polygenic risk score were associated with higher odds. No significant association was observed between PA and PD. In interaction analyses, we found statistical evidence for an interaction between polygenic risk of PD and the following environmental/lifestyle factors: T2D (p = 6.502 × 10-8), PA (p = 8.745 × 10-5), BMI (p = 4.314 × 10-4), and tobacco use (p = 2.236 × 10-3). Although BMI and tobacco use were associated with lower odds of PD regardless of the extent of individual genetic liability, the direction of the relationship between odds of PD and T2D, as well as PD and PA, varied depending on polygenic risk score. INTERPRETATION: We provide preliminary evidence that associations between some environmental and lifestyle factors and PD may be modified by genotype. ANN NEUROL 2024;95:677-687.

Multi-ancestry genome-wide association meta-analysis of Parkinson's disease.

Although over 90 independent risk variants have been identified for Parkinson's disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson's disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations.

The non-coding GBA1 rs3115534 variant is associated with REM sleep behavior disorder in Nigerians.

Background: Damaging coding variants in GBA1 are a genetic risk factor for rapid eye movement sleep behavior disorder (RBD), which is a known early feature of synucleinopathies. Recently, a population-specific non-coding variant (rs3115534) was found to be associated with PD risk and earlier disease onset in individuals of African ancestry. Objectives: To investigate whether the GBA1 rs3115534 PD risk variant is associated with RBD. Methods: We studied 709 persons with PD and 776 neurologically healthy controls from Nigeria. The GBA1 rs3115534 risk variant status was imputed from previous genotyping for all. Symptoms of RBD were assessed with the RBD screening questionnaire (RBDSQ). Results: The non-coding GBA1 rs3115534 risk variant is associated with possible RBD in individuals of Nigerian origin (Beta = 0.3640, SE = 0.103, P =4.093e-04), as well as after adjusting for PD status (Beta = 0.2542, SE = 0.108, P = 0.019) suggesting that this variant may have the same downstream consequences as GBA1 coding variants. Conclusions: We show that the non-coding GBA1 rs3115534 risk variant is associated with increased RBD symptomatology in Nigerians with PD. Further research is required to assess association with polysomnography-defined RBD.

Evaluating the performance of polygenic risk profiling across diverse ancestry populations in Parkinson's disease.

Objective: This study aims to address disparities in risk prediction by evaluating the performance of polygenic risk score (PRS) models using the 90 risk variants across 78 independent loci previously linked to Parkinson's disease (PD) risk across seven diverse ancestry populations. Methods: We conducted a multi-stage study, testing PRS models in predicting PD status across seven different ancestries applying three approaches: 1) PRS adjusted by gender and age; 2) PRS adjusted by gender, age and principal components (PCs); and 3) PRS adjusted by gender, age and percentage of population admixture. These models were built using the largest four population-specific summary statistics of PD risk to date (base data) and individual level data obtained from the Global Parkinson's Genetics Program (target data). We performed power calculations to estimate the minimum sample size required to conduct these analyses. A total of 91 PRS models were developed to investigate cumulative known genetic variation associated with PD risk and age of onset in a global context. Results: We observed marked heterogeneity in risk estimates across non-European ancestries, including East Asians, Central Asians, Latino/Admixed Americans, Africans, African admixed, and Ashkenazi Jewish populations. Risk allele patterns for the 90 risk variants yielded significant differences in directionality, frequency, and magnitude of effect. PRS did not improve in performance when predicting disease status using similar base and target data across multiple ancestries, demonstrating that cumulative PRS models based on current known risk are inherently biased towards European populations. We found that PRS models adjusted by percentage of admixture outperformed models that adjusted for conventional PCs in highly admixed populations. Overall, the clinical utility of our models in individually predicting PD status is limited in concordance with the estimates observed in European populations. Interpretation: This study represents the first comprehensive assessment of how PRS models predict PD risk and age at onset in a multi-ancestry fashion. Given the heterogeneity and distinct genetic architecture of PD across different populations, our assessment emphasizes the need for larger and diverse study cohorts of individual-level target data and well-powered ancestry-specific summary statistics. Our current understanding of PD status unraveled through GWAS in European populations is not generally applicable to other ancestries. Future studies should integrate clinical and *omics level data to enhance the accuracy and predictive power of PRS across diverse populations.

Isolated rapid eye movement sleep behaviour disorder (iRBD) in the Island Study Linking Ageing and Neurodegenerative Disease (ISLAND) Sleep Study: protocol and baseline characteristics.

Isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is a sleep disorder that is characterised by dream enactment episodes during REM sleep. It is the strongest known predictor of α-synuclein-related neurodegenerative disease (αNDD), such that >80% of people with iRBD will eventually develop Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy in later life. More research is needed to understand the trajectory of phenoconversion to each αNDD. Only five 'gold standard' prevalence studies of iRBD in older adults have been undertaken previously, with estimates ranging from 0.74% to 2.01%. The diagnostic recommendations for video-polysomnography (vPSG) to confirm iRBD makes prevalence studies challenging, as vPSG is often unavailable to large cohorts. In Australia, there have been no iRBD prevalence studies, and little is known about the cognitive and motor profiles of Australian people with iRBD. The Island Study Linking Ageing and Neurodegenerative Disease (ISLAND) Sleep Study will investigate the prevalence of iRBD in Tasmania, an island state of Australia, using validated questionnaires and home-based vPSG. It will also explore several cognitive, motor, olfactory, autonomic, visual, tactile, and sleep profiles in people with iRBD to better understand which characteristics influence the progression of iRBD to αNDD. This paper details the ISLAND Sleep Study protocol and presents preliminary baseline results.

Effectiveness of interactive workshops to raise awareness of the neurological harms associated with nitrous oxide use: a cross-sectional study.

BACKGROUND: The Royal London Hospital, East London, receives a case of nitrous oxide (N2O) myeloneuropathy roughly every 9 days. No formal education programme is widely available to warn young people of the risks of recreational N2O use. Our aim was to develop and evaluate the effectiveness of workshops focusing on the neurological risks of N2O, with the primary outcome to increase awareness of these risks among young people. METHODS: For this cross-sectional study, the workshop content was piloted with over 200 people at a community event, received input from a person with lived experience, and then piloted with a youth group, all in east London, UK. Between Oct 10, 2022, and April 11, 2023, 32 workshops were delivered to 984 young people in schools and youth groups in east London. The workshop included three interactive activities exploring how and why N2O causes neurological damage. An online anonymous questionnaire including free text and 5-point Likert scale answers was provided after each workshop. The HRA ethical toolkit and NIHR INVOLVE guidance were consulted, and NHS ethics approval was not required. FINDINGS: 396 (40%) of 984 workshop participants completed the questionnaire. The median age bracket of attendees was 13-15 years. 38 (10%) of 396 respondents reported past use of N2O, while 24 (6%) did not divulge use or non-use. Self-perceived likelihood of use was reduced after the workshop, with 261 (66%) very unlikely to use N2O before the session compared with 290 (73%) after the session. 238 (60%) respondents reported an increase in self-perceived knowledge of the risks after the session. When asked about their understanding of the risks of N2O, 206 (52%) relayed something related to N2O causing neurological damage. 327 (83%) respondents found the workshop useful. INTERPRETATION: This work highlights the feasibility of raising awareness among young people of N2O-myeloneuropathy in this workshop format. Limitations included difficulties involving many participants with lived experience in design, an absence of pre-existing interventions to compare against these workshops, and that data collection from young people required pragmatic, short questions. Overall, this work supports larger-scale preventive approaches to N2O-myeloneuropathy, such as a national education programme. FUNDING: Queen Mary Centre for Public Engagement Small Grant Fund.

Bidirectional relationship between olfaction and Parkinson's disease.

Background: Hyposmia (loss of smell) is a common early symptom of Parkinson's disease (PD). The shared genetic architecture between hyposmia and PD is unknown. Methods: We leveraged genome-wide association study (GWAS) results for self-assessment of 'ability to smell' and PD diagnosis. Linkage disequilibrium score regression (LDSC) and Local Analysis of [co]Variant Association (LAVA) were used to identify genome-wide and local genetic correlations. Mendelian randomization was used to identify potential causal relationships. Results: LDSC found that sense of smell negatively correlated at a genome-wide level with PD. LAVA found negative correlations in four genetic loci near GBA1, ANAPC4, SNCA, and MAPT. Using Mendelian randomization we found evidence for strong causal relationship between PD and liability towards poorer sense of smell, but weaker evidence for the reverse direction. Conclusions: Hyposmia and PD share genetic liability in only a subset of the major PD risk genes. While there was definitive evidence that PD can lower the sense of smell, there was only suggestive evidence for the reverse. This work highlights the heritability of olfactory function and its relationship with PD heritability and provides further insight into the association between PD and hyposmia.

The Emergence and Progression of Motor Dysfunction in Individuals at Risk of Parkinson's Disease.

BACKGROUND: PREDICT-PD is a United Kingdom population-based study aiming to stratify individuals for future Parkinson's disease (PD) using a risk algorithm. METHODS: A randomly selected, representative sample of participants in PREDICT-PD were examined using several motor assessments, including the motor section of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)-III, at baseline (2012) and after an average of 6 years of follow-up. We checked for new PD diagnoses in participants seen at baseline and examined the association between risk scores and incident sub-threshold parkinsonism, motor decline (increasing ≥5 points in MDS-UPDRS-III) and single motor domains in the MDS-UPDRS-III. We replicated analyses in two independent datasets (Bruneck and Parkinson's Progression Markers Initiative [PPMI]). RESULTS: After 6 years of follow-up, the PREDICT-PD higher-risk group (n = 33) had a greater motor decline compared with the lower-risk group (n = 95) (30% vs. 12.5%, P = 0.031). Two participants (both considered higher risk at baseline) were given a diagnosis of PD during follow-up, with motor signs emerging between 2 and 5 years before diagnosis. A meta-analysis of data from PREDICT-PD, Bruneck, and PPMI showed an association between PD risk estimates and incident sub-threshold parkinsonism (odds ratio [OR], 2.01 [95% confidence interval (CI), 1.55-2.61]), as well as new onset bradykinesia (OR, 1.69 [95% CI, 1.33-2.16]) and action tremor (OR, 1.61 [95% CI, 1.30-1.98]). CONCLUSIONS: Risk estimates using the PREDICT-PD algorithm were associated with the occurrence of sub-threshold parkinsonism, including bradykinesia and action tremor. The algorithm could also identify individuals whose motor examination experience a decline over time. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Potential Protective Link Between Type I Diabetes and Parkinson's Disease Risk and Progression.

BACKGROUND: Epidemiological studies suggested an association between Parkinson's disease (PD) and type 2 diabetes, but less is known about type 1 diabetes (T1D) and PD. OBJECTIVE: This study sought to explore the association between T1D and PD. METHODS: We used Mendelian randomization, linkage disequilibrium score regression, and multi-tissue transcriptome-wide analysis to examine the association between PD and T1D. RESULTS: Mendelian randomization showed a potentially protective role of T1D for PD risk (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.94-0.99; P = 0.039), as well as motor (OR, 0.94; 95% CI, 0.88-0.99; P = 0.044) and cognitive progression (OR, 1.50; 95% CI, 1.08-2.09; P = 0.015). We further found a negative genetic correlation between T1D and PD (rg = -0.17; P = 0.016), and we identified eight genes in cross-tissue transcriptome-wide analysis that were associated with both traits. CONCLUSIONS: Our results suggest a potential genetic link between T1D and PD risk and progression. Larger comprehensive epidemiological and genetic studies are required to validate our findings. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Nitrous oxide-induced myeloneuropathy: a case series.

BACKGROUND: Nitrous oxide (N2O) is the second most common recreational drug used by 16- to 24-year-olds in the UK. Neurological symptoms can occur in some people that use N2O recreationally, but most information comes from small case series. METHODS: We describe 119 patients with N2O-myeloneuropathy seen at NHS teaching hospitals in three of the UK's largest cities: London, Birmingham and Manchester. This work summarises the clinical and investigative findings in the largest case series to date. RESULTS: Paraesthesia was the presenting complaint in 85% of cases, with the lower limbs more commonly affected than the upper limbs. Gait ataxia was common, and bladder and bowel disturbance were frequent additional symptoms. The mid-cervical region of the spinal cord (C3-C5) was most often affected on MRI T2-weighted imaging. The number of N2O canisters consumed per week correlated with methylmalonic acid levels in the blood as a measure of functional B12 deficiency (rho (ρ)=0.44, p=0.04). CONCLUSIONS: Preventable neurological harm from N2O abuse is increasingly seen worldwide. Ease of access to canisters and larger cylinders of N2O has led to an apparent rise in cases of N2O-myeloneuropathy in several areas of the UK. Our results highlight the range of clinical manifestations in a large group of patients to improve awareness of risk, aid early recognition, and promote timely treatment.

The Views of Patients with Isolated Rapid Eye Movement Sleep Behavior Disorder on Risk Disclosure.

BACKGROUND: Isolated rapid eye movement sleep behavior disorder (iRBD) is associated with an increased risk of Parkinson's disease and other synucleinopathies. There is no consensus about disclosure of this risk to patients with iRBD. OBJECTIVE: The objective of our study was to assess the experiences of risk disclosure in a group of patients with iRBD and their views on what, when, and how this should be done. METHODS: A survey was administered to patients with iRBD to explore their experiences and views on risk disclosure. RESULTS: Thirty-one patients with iRBD (28 males; mean age, 70 [SD 8.7] years; mean disease duration, 8.7 [SD 6.4] years) were included. A third reported they had not been informed about the link between iRBD and other conditions by clinicians at diagnosis, but 90% would have liked to have received prognostic information, and 60% indicated that this should happen at the point that iRBD was diagnosed. Most participants wanted this information to come from the clinician diagnosing and treating iRBD (90.3%). Almost three-quarters (72.2%) had searched for this information online. CONCLUSIONS: Patients with iRBD mostly wished to have received information regarding the potential implications of iRBD when the diagnosis was made. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.